'neurometabolic wear and tear
This is what happens in depression, dendritics shafts in the
hippocampus shrink, some thinking this leads to a vicious cycle because
the hippocampus can play an important role in inhibiting the PVN, the
"first" region that sets off the stress response. Long term major
depression can markedly shrink the hippocampus and there are many
people around with untreated moderate depression which may be paving
the way to full blown depression in their latter years.
Perhaps there might be two or three variants of a such signature
(due to a small assortment of different allels). Just my guess.
Don't know but suspect it is true. Whatever signatures exists will be
not be finally known to have a more global understanding of CNS
function. At present we stab in the dark. Well you've got to start
somewhere.